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>> rose: welcome to our program. tonight a charlie rose special edition. in the tent episode of our brain series we look at the disordered brain. >> today we are going to discuss these neurological diseases and we're going also see that a fundamental difference between neurology an psychiatry is that by and large, we don't know very much about the anatomical underpinnings of most psychiatric disordered. we don't know the neurocircuit trie responsible for schizophrenia and by polar disorder swrechlt good insight into the neurocircuitry underlying most neurological disorders. >> rose: the tent episode of the charlie rose brain series underwritten by the simons foundation coming up. >> the charlie rose brain series is about the most exciting scientific journey of our time it understanding the brain. the series is made possible by a grant from the simons
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foundation. their mission is to advance the frontiers it of research in the basic sciences and mathematics. funding for charlie rose was provided by the following:
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captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> rose: tonight we continue our journey through the fascinating world of the human brain when working properly the brain performs sophisticated tasks smoothly and easily. it allows us to move and to speak and to interact with our surroundings, requiring only minimal amount of effort. but when the brain is damaged, its true complex sit revealed. our subject this evening is the neurological disorders. these include parkinson's disease. stroke. huntington's disease and spinal chord injury. these conditions have taught us more about our brain than any other kind of brain disease. through parkinson's we have learned about movement. through stroke we have
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learned about speech. and through spinal cord injuries we have learned how thoughts give rise to actions. neurological diseases have been a topic of research for sent yees but-- century bus only recently have we developed effective treatments. this evening we will meet a group of scientists who have developed ways to repair or bypass the disordered brain. john done o hew. his work allowed paralyzed patients to move and communicate using only their thoughts and a machine called a brain computer interface. he is a professor at brown university and co-founder of a company called cybernetics. john craw krauer, his work exfloor-- craw quarter, how movement is recovered following a stroke. he is an associate professor of neurology and neuroscience at columbia. nancy bonini. she studies the genetic basis of neurological disease by performing experiments on fruit flies. she is a professor at the university of pennsylvania and the howard hughes medical investigator. and joining me from atlanta
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is malion delong, an expert on parkinson's disease and a pioneer in the growing field of deep brain stimulation. he is a professor of neurology at emer university school of medicine. and once again my cohost is dr. eric kandel. as you know he is a nobel laureate, professor at columbia university and a howard hughes medical investigator the. i am pleased once again to have him here to help me understand all about the brain. so welcome back. >> thank you. are you doing very well understanding the brain. >> rose: and what a journey it is. so tell me about today, the disordered brain. >> well, last time we discussed psychiatric disorders. today we are going to cause neurological disorders. the bulk of the disorders of the brain so one of the first things you want to explore is how are they different from one another. what is the logic of neurological as compared to psychiatric disorders there are two fundamental differences. one in the nature of the sim
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poll-- symptoms and two an anatomical location. in terms of symptoms, there is overlap but from a simplified point of view you could say that psychiatric disorders deal with enhancements, exaggerations of our every day life. we all feel despondent periodically. we all feel hopeless and worthless when an experiment doesn't work. and this is an extension what you see in depressed people. the mirror image, euphoria we experience when thing goes well. when we have a wonderful round table discussion. and we see a dramatic extension of that in manic disordered. and even schizophrenia, hallucinations and illusions we have examples of that in our dreams. by contrast, neurology differs in two ways in terms of symptomatology. first we see fragmentations of symptoms it t in parkinson's disease we see a
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dramatic slowing of movement. but in addition we see the appearance of behaviors that we don't normally see otherwise. with a lesion of the parietal lobe we see neglect of a whole side of the body. just absolutely remarkable. a denial that it's there. but perhaps an even more fundamental distinction is anatomical. we know very little about the anatomical location of psychiatric disorders. one of the what are the brain regs involved with schizophrenia and depression well. are just beginning to discover that we have an underpinning of near lodge came diseases. and we've known this for years. when i was a medical institute in the 1950s clinical neurology was known as the medical discipline that could diagnose everything and treat nothing. this has changed dramatically. as we are going to learn on this program, there are major new treatments coming along in neurology that have
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revolutionized treatments in various neurological disorders. parkinson's disease. stroke, even spinal cord transsections. now one of the interesting things about it, this progress again is involved finding out more about the location of specific neurological diseases. its location, location, location that counts in the brain. and the history of how we localize functions itself is so fascinating. it began around 1860 with paul broker. paul broker was interested in disorders of language. aphasias and much of what we learned about the early localization of functions came from studies of language disorders. broker encountered a very interesting patient one day. he had an aphasia, a language difficulty which took the form of the fact that the patient could not express himself very satisfactory in language. he could understand language
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perfectly well but he couldn't make himself understood. this is not simply a paralysis of the vocal cords, cohum perfectly well. moreover he couldn't write language. he just could not express himself in language. >> rose: but counder stand. >> he could understand perfectly well. when died and came to autopsy, broker examined him and found a lesion in the front of the brain. he wanted to talk about this to his colleagues. so he had to give it a name and in all modesty he named it after himself. broker's area. he then encountered eight other patients that had a similar aphasia. they could not express themselves in language but could understand perfectly well. when they died and came to autopsy, he found invariably they had a lesion in the front of the brain. and invariably the legs was on the left side. -- the lesion was on the left side. this caused him to realize one of the major insights we have in the biology of the brain. we speak, he said, with our left hemisphere. the left hemisphere specializes speech. this galvanized the
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scientific community. people began to look for other localizations of functions. and ten years later, fritz and hesic two german investigators working on dogs found that there is a systemic representation of body movements on the surface of the brain called the motor cortex or the motor strip. if you stimulate one part of the motor strip your face moves. if you stimulate another, your arm moves. stimulate another, the leg moves. there is a estimateic representation of your body movement on the surface of the brain. this is extraordinarily exciting. and a few years later, in about 1875, another giant came on the scene, carl-- an extraordinary guy. a couple of years out of medical school before he was 30 years old, he made a fantastic discovery. he found another language deficit, another aphasia but this was a difficulty in understanding language, not in expressing it. so this patient could express language perfectly
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well but he couldn't understand language. when he came to autopsy, he was examined and found the lesion not in the front of the brain but in the back of the brain. >> rose: the left hemisphere in the back. >> the left hemisphere but in the back. so again he had to name it so he could speak to other people about it and he called this-- area. >> rose: right. >> and he said to himself, isn't iting interest. we are dealing with a complex function like language. this is not localized to a single region. this involves at least two regions. one for understanding language. and one for expressing it. like a and we look to see where they were located, he realized that the vertic area, the area he worked on was at the back of the brain. this is where senseory information comes in. >> rose: understanding language ask where it comes in. >> exactly, information from read organize hearing feeds into the back of the brain into the auditory cortex and visual cortex. these two areas converge on
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to vertic's areas and put that visual information in the auditory information in a code for understanding langge. he also knew there was a connecting pathway called the occuforsiclus. so the information goes from the senseory areas to vernica's area to the-- to broker's area. >> rose: what kind of connection is that. >> this is a pathway, anatomical pathway. and that question made him realize a very profound thing. he said i bet you one can get an aphasia, a language deficit without damaging broker's area or vertica area by simply interrupting the pathway. >> rose: pathway. >> you got it, you interrupting the pathware between the two. on his old circumstances the patient understands. the patient can speak. but there is no connection between the two. it is like an occasional presidential press
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conference. information comes in, information comes out but there need not be a connection between the two. >> rose: all right so let me ask about this too. where is the genetic understanding taking this? >> well, we have several areas in which we made terrific progress, okay so number one, in addition to understanding the areas that are involved in speech, we have a very good understanding of the areas involved in the movement, okay. and malion delong has discovered still another area important in the wasal ganglia for parkinson's disease and he has collaborated and used deep brain stimulation to produce dramatic improvements in parkinson's disease. john donoghue has done something equally remarkable. you mentioned the fact that there are specific areas that involve the movement, the motor strip. they fire in a characteristic way when you pick up a glass of water. he realized he could use that information to drive a
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computer. so if you want to pick up a glass but you are paralyzed so you can't do it, that information from your motor cortex can go on to a computer that can drive a robot to pick up the glass of water for you and bring it to your mouth. >> rose: this is extraordinary. it must have enormous potential. >> it has tremendous potential. >> rose: if you can think, you can do. >> exactly it also gives you additional confidence in the fact that we are reading the brain correctly. john krakauer is on the verge of revolutionizing the treatment of stroke. he thinks the period of plasticity of stroke is greater and the question that you originally raised there is a lot of genetics that we now understand about these neurological disorders. and nancy bonina has taken these genes that are disorder-- disordered in neurological, into a system that we can study mechanism of pathogenesis. how does the disease come about. so we are going to have a marvelous evening together. >> rose: okay, all that you wanted to know about
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neurological diseases, the disordered brain, both neurological and psychiatric. we go now to our panel. let me begin with you, john. tell me sort of a primer on these neurological disorders and hoy we approach them. >> right. so i think following on from what eric said, the study of neurological diseases is important for two related reasons. one, is that they help us gain i sight into how the normal brain is put together. because in every day life our behavior seems so seamless, o so easy. it's not until we vb an injury to the brain that we suddenly see how, in fact, the seamless behavior is made up of component pieces. and so we can gain insight into those components and how they actually organize in the brain in neurological disease. and in the second related area is by studying neurological disess we can get an insight into treatment. so i would like to sort of give two examples of the kind of insight we can gain from studying neurological patients.
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and i'm going to use this brain as an example. a big debate raged in the 19th century between two camps. one camp that thought that brain function was divided up into localized components and another camp thought the brain did everything holisticically. all right. and interesting as that debate goes on today but and the reason for this debate was because it all depended what kind of disease you decided to study. so for example if you get a stroke in this motor strip here, you develop a paralysis in the limbs on the upper side of the body. but otherwise are you okay. you think okay. your language is okay. it's just the limb on the opposite side of the body that is affected is so what is a very strong case for highly localized function. fwlu are other kinds of lesion that cause a much more diffuse broad set of abnormalalities which made it very difficult to believe that all of those could be actually controlled by one region. so for example you could get something called neglect especially when you affect the right side of the brain and you get the inferior part of what is called the
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parietal lobeal. these patients have difficulty oriented, attending and acting to stimuli in one half of visual space or on one half of their body. in this particular case, the left side. so for example if you touch things after this lesion here on their left side, you ask them where are you touching them, they will say my right. when you walk into the room from the left, they will go hello, and turn their head to the right. okay. so profound cognitive problems caused by a fairly focal lesion. so in other words, in some case the processing is local and you get a focal effect and that is why some people thought it was all localized. in another case you have a focal lesion that has diffuse effects, could have a knockdown effects to other regions and you get a more global abnormalality. so you can see by continuing to study patients with imaging techniques that allow us to see this architecture we can learn fundamental principless about how the brain is put together. so parkinson's patients have a part of the syndrome is
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brady kin esia, they move slowly. so after question, one tends no the to ask. why do parkinson's patients mover more slowly. and the converse question is why do we move at the speed that we do. so i would like to do a little experiment to show that. if each of you reaches for your glass of water. you will find that all of us pretty much reach at the same speed. so on the one hand you voluntarily decided to reach for the glass. but on the other hand you unconsciously picked a speed which was very similar to all of ours. a whand we think might be happening is that they have a different balance between how much effort is required to reach the glass and how worthwhile it is to reach the glass, and there unconsciously the balance is moved towards it being too effortful to move fast to get it in the same time that we do. >> give us a sense of sort of what the history of what we have understood and how we have treated parkinson's and where we are today. >> james parkinson in 1817
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described parkinson's. it was the first description. slowness of movement. characteristic tremor and the shuffling gait. in fact he called it the shaking palsy. because of the tremulousness and slowness. palsy meaning weakness. he did not name it after himself. it was 150 years from that time, roughly, that the first really effective treatments were developed. and ironically, these were not medical but surgical. neurosurgical procedures. neurosurgeons desperate to find treatment for patients with uncontrollable, excessive tremulousness were able to identify largely by trial and error specific regions in parts of the deep brain circuits. and this involves the basal ganglia and the region called the thalamus. but in the 60s there were
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remarkable series of discoveries. the first was the presence of a substance called dopamine within the brain. and particularly in the basal ganglia. and then in rapid succession, the evidence that it was depleted in brains of patients who were at autopsy with parkinson's. these two discoveries led to the attempts to replace that substance by giving a drug called levadopa, a precursor of dopamine. and taken and absorbed and actually reaches the brain. and this was viewed as a cure. it was a matter of time, though, that the other foot dropped, so to speak. and began to realize that with, after the honeymoon period of a number of years, often patient was develop involuntary movements. we call them diskin esias, or they would have what we call motor fluctiations where the medicine would wear off abruptly.
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and these combination of motor fluctuationsing sometimes failure to respond and the diskinesias would be very disruptive of movement. and this called for really alternative approaches. during the '70s and '80s there was a remarkable series of, i would say studies and progress in understanding the motor-- better its motor system, an all-- anatomy and physiology. and one of the most important thing i think in relevant to parkinson's was the understanding that the basal ganglia which were depleted of dopamine were doing something more than just providing some substrate for movement. in fact, it was commonly believed at that time that the basal ganglia were primarily movement because of the association that disturbances and movement and basal ganglia dysfunction well. were able to show that, in
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fact t was a restricted part of the basal ganglia that were really involved with movement and that other regions were involved with higher function. the key to finding this, understanding the mechanism of this was actually to lesion, to destroy a small part of the motor circuit within the basal ganglia. and this a region call kd the subphalamic nucleus. details are not as important. >> it was just a fantastic advance to realize that this area which is by and large effected in the basal ganglia had a central role in the control of movement and in parkinson's disease. and that's what lead you really to start thinking about using deep brain stimulation for that. >> we were at first, and i think others, most concerned not to lesion the sub phalmic nucleus. it was really alan-- discovery when he applied it to the sub phalmic nucleus that was so important in the development of this new
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approach. by the 1990s, deep brain stimulation had virtually replaced all approaches to treating parkinson's disease. this was the great advantage of deep brain stimulation was the nondestructive reversible and adjustable nature of this treatment. i'm going to show you one of our first and-- or earliest patients. this was our 17th patient who had received deep brain stimulation. and this was in 1997. and we'll let this roll. >> the disease had gotten so bad that sometimes her muscles froze completely making her face almost expressionless. and her legs almost useless. the woman who once was always on the go could barely move. confined to a wheelchair. >> do you ever wake up in the morning and forget that you have parkinson's for a moment or two. >> not now.
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not recently. because my every waking hour is terrifying. >> but on the morning of the surgery cybil was confident. even as nurses fitted her with a head frame to help guide surgeons during the operation. and as they wheeled her to the x-ray, she was in good spirits. >> deep brain stimulation comes down to one thing. location. to help pinpoint the region of cybil's brain where he would be working neurosurgeon roy bakay used magnetic resonance centre imaging. finding the target area holds the key to sib will-- cybil's future. if the stimulator sim planted correctly she may finally be free of the tremor and pain that have haunted her for years. but if the place suspect off, the results could be devastating. >> finally, the doctors think they have placed the electrode in the exact location that will help cybil. when they turn on the stimulator she suddenly shows an astonishing range of motion. in her legs and hands. >> you can lift your leg up at all. >> there you go.
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up and down. drop it down now, now pick it up. great. >> she couldn't do that before. >> how about the hand. you can open and close your hand for me now. good. okay. >> and when the doctor turns off the stimulation, cybil's tremor and stiffness return. >> i turned off the stimulator. don't be worried, okay. request you move your ankle up and down. it's hard to do forer her. >> it was only a month after her second surgery when we caught up with cybil again. >> when i talked to you before you had any surgery, one of your biggest problems was that you couldn't tush over in bed. >> i was really concerned about that. but now i roll back and forth. (laughter) >> you can't stop me now. >> now the woman who never wanted to slow down doesn't have to. >> what can you do now that you can't do before.
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>> oh,. >> look at her, look at that. >> cybil and alvin had hoped for a lot from the surgery but the outcome was better than they could have imagined. >> the underline what that tape shows us. >> i think the most important thing is that it shows the clinical benefits and it shows the profound effect on quality of life. cybil, this simple video shows that better than any. >> it also shows how scientific the treatment become. because they first introduced the electrode for deep brain stimulation on one side of the brain. and it stopped the tremor on one side of the body. and then in order to control the other side, they second, as an afterthought put in the electrode on the other side and stoped it on the second side of the body. so the patient now is free of tremor. and she moves from being essentially paralyzed to jumping and dancing around with her family. it's an extraordinary improvement.
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>> rose: does it work on everybody and what have we learned about it? >> yeah, that's a very important point. this does not work for everybody. and the's not a cure. it's a completely symptomatic treatment. and if the battery should fail or the wires become disconnected, can happen, but not common, the benefit is lost almost immediately wrz let me turn to nancy and talk about genes and how they are involved in the diseases we're talking about. >> right. so another approach to get towards these diseases is to take a very basic research approach and use animal models. and an example of an animal model which is the fruit fly has powerful genetic approaches. so for many of these human neurodeagain rative diseases, in fact for many human diseases there are gene inherited forms as well as the more spontaneous so-called sporadic forms. but we have ways in the familyial situation where a clear gene is involved to get that gene and then we
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can study that gene. so for parkinson's disease, for example, one of the key genes that was identified is the gene called alpha cynucleon it is mew tated in rare inherited forms of parkinson's disease. well, it turns out that alpha cynucleon also accumulates abnormalally in the brain of all parkinson disease patients. this has allowed the idea that even though you find these genes through these rare inherited forms, studying-- they are going to tell you about the disease in general, even though most of the disease is sporadic. so with a gene, you can then study the ways in which that gene may cause disease. and that's called studying the pathogenesis. and animal models are really key experimental tools in this. and there are many different types of animal models that she's actually touched on in this series such as the them o todays, or the mouth and i'm going to talk about the system that we use, the
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basic fruit fly so the fruit fly was really used and developed as an experimental organizism by thomas hunt morgan at columbia university. and he was interested in basic aspects of chromosome and heredity. later see more benzer he opened up the world of the brain and the fly and he focused on genes that were involved in behavior. and just like malion talked about there are regions of the brain that are isolated, but they also connect to other regions of the brain, greens don't work on their own but genes work in a network with other genes. and these are called gene pathways. so in fact we now know that for many process cease not only genes but entire gene pathways are shared between flies and humans. so that means that he with can then take that gene and study it and ask how it may be functioning. and hope to learn not only about flies but really what we are interested in.
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we're interested in people, in humans. right. and so this, the fly has been classically used to approach development and then it's more recently become very popular for behavior. and we decided well, why not try with human disease. so the idea would be that whereas these diseases in humans can take decades for their onset, in flies we can give a fly a copy or what it looks like to have parkinson a disease in days to weeks. so we can, so we can grow many flies and we can speed up the whole process in order to really study that mechanism so on the next slide shows sort of a section through the fly brain where we're studying some aspect of parkinson a disease so an idea is when we have the gene, what should-- like alpha cynucleon we can put that gene into flies and then ask can we get an effect in the flys that looks like parkinson's disease. as malion talked about,
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dopamine is really important in parkinson's disease. and so we can ex-- express that parkinson disease gene in the-- so the top panel shows clusters of dopamine neurons in the fly brain normally and what happens when we put in alpha cynucleo in is seen in the panel so we see fewer of those cells staining for this marker for dopa-- if we express it, they become compromised and sick and some people you can even see movement disorders in these flies. so in fact, by expressing this gene that is associated with human parkinson a disease we can get effects in the fly that-- fly that look like core effects of parkinson a disease so i would like to show another example that is showing an effect on climbing behavior. so this is using a gene in the fly that is involved in als. so als is another reall
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really-- another-- lou geric's disease. lou gehrig's disease it is another very debilitating disease. and it leads to loss of voluntary movement control and eventually paralysis. >> this is what tony jett suffers from. >> right. so if we look at the behavior of normal flies. normal flys will climb upwards. they have this robust negative geo tactic response but the flys that are defect piv in this human als gene, these flys are alive and they're moving but they can no longer climb. so this is a remarkable example of sort of a fundamental copy or we're mimicking the disease in the fly situation. so of course in the real laboratory we would take a very comprehensive approach to this. so we look at many, many different aspects of what it looks like in the fly to express one of these genes. and we're asking how many features look similar to the human situation so that we
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can say how well does the fly show the fundamental features of that disease. and so in this situation, we're sort of using the power of conserved pathways and conserved genes in order to approach the really complicated problem of human disease. >> let me now move to john donoghue and talk about brain computer interface and give me a history of that too and where we are today. >> sure, charlie. what i would like to go is go back to the idea of localization and brain circuits and not the brain circuit for language but the one for arm movement and how we have taken the fundamental discoverys in that area and turned it into the ability to help people who are paralyzed move again. so first i would just like to show that there are-- that what goes wrong in paralysis so basically this in this slide it shows two kinds of major routes of paralysis. one is that the central motor pathways are disrupted. and the other is the peripheral motor path waste are disrupted. in both of those cases the brain is intact and
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functioning but it's connection to the outside world is broken. and what we are trying to do is we would be interested in doing is reconnecting the brain to the outside world. we can't fix those pathways. we don't know how to fix them yet but inside-- instead of using a biological repair we could use a physical repair that is truly wires and fibre-optic connections. so to do that we relied on some very fundamental knowledge. one is the idea of localization. eric brought up the idea that there is this region in the motor cortex. there is a region near the top of your head about the size of a quarter that controls your arm. and that we've known since about the 1870s. this was a great area of discovery. about you interestingly, what the neurons in that area did was unknown until about the 19th-- 1960s when we started putting microelectrode in the brain. and listening in on a single neuron and asking what it did. if you played the video, i think i have a single fewer on, you can hear the popping. >> it's very exciting.
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>> so this is the truth, we can hear the crackling noise so this is the true romance of the neurofisiologist is our job as neurofisiologists to try and make sense of that. so you are actually listening to a cell that is related to movement. and those little popping noises are called spikes. and that's the code of the brain. and neurofisiologists try to decode the brain and page sense of movement. and from studying behaving animals we learned that the motor cortex, is very interested in producing commands of when to move and which way to move, left or right so we had some insight from these years of experiments. for about the next two decades we explored those areas and we learned that really this information was encoded not in the single nearon but in populations, much like the information in a symphony is not encoded by the second violinist but you have to listen to the whole orchestra. and what was seriously lacking was the ability to try and capture many cells at once like listening to the whole symphony.
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so we developed an electrode array that is instead of one, a tiny implant of many electrodes that is shown on this slide. it's actually something about the size of a baby aspirin. it's implanted permanently in the arm area of motor cortex and that it comes outside and the signals are brought to the outside in its current version so it's very tiny, not even the size of a penny. at that point we said well here we have technology that allows us to peer into the brain. we have an understanding at least a primitive understanding of what that part of the brain, the arm area of the motor cortex is trying to do. we could, in fact, take people who are paralyzed, that is able to think about movement but not able to move and connect their brain back up to the outside world so i guess what could be seen as a rather bold step but we thought fda approval and we were approved by the fda to study a small number of severely paralyzed people, tetra pledgeics they can't move their arms and legs. and we implanted five people so far in this small trial.
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and i think just by illustration, i will show you that one of the first patients his name is matt. he is playing a video game here. he is supposed to hit those things that, those are treasure chests and avoid the square wris actually goblins. a video game called he man. would you say he was playing that video pretty well but not great. but in fact matthew was injured in his cervical spinal cord. is completely disconnected his brain from his entire body. he has the chip in his arm area of motor cortex and merely by thinking about moving, he is actually making that curser move. >> amazing. >> it's stunning. >> that you can -- >> but again, it's a true example of taking the information from basic science. we had all the pieces. and we just put it together so that we could reconnect the body to the outside world. >> and what are the possibilities of this? >> well, will you hear more about the possibilities, i think. we want to give a couple examples that i think take us s so we've sort of stepwise gone through. so one step is you can control something physical. so we thought of something physical, a mechanical hand
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so matthew can't control his own hand so we brought a mechanical hand. and here we are seeing a video of matthew thinking about hoping and closing a hand and there he is opening and closing his hand. he had a profound effect on him because it was the first time in years that he had actually moved anything physically himself. he is doing it entirely with his mind. then to extrapolate that a bit further. we asked could you control something practical like a wheelchair. this is actually a lady who has what is called a brain stem stroke. a little bit above the spinal cord. she is not only unable to move, she can't speak. but what she is doing here is using brain gait, this chip to control that wheelchair so it's wireilessly beamed over to the wheelchair and actually the control system is that little computer mounted on the wheelchair. i had asked her to drive the wheel care over to the door. she had practiced for about five minutes before this. and here she is sort of not very gracefully, but driving the over towards the door. and you will see it progress up over to the door. and of course, you know, the control isn't good enough,
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we wouldn't have her in the wheelchair, we just had her do it remotely. >> so at this point we have shown in each of several different disorders that is correct includes spinal chord injury. in stroke. and even in to als patients, it's possible to decode the brain with, sense the signals, decode the brain and connect them to devices, but these are all demonstrations. we are not there yet where these are available for every day use but matthew actually record some of his comments about his views on the technology. and i think if you, i think this video will just, can narrate it and tell you what he thought of the technology. >> i envision this giving me more independence as far as changing the television, opening my shades, turning on my lights. or what the nurses have to come down and do for me. so it will give me t will give me a sense of
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independence. not, you know, not as much as i like but it will give me some independence. and for me that would be wonderful. >> but it's also so wonderful about this is not only the clinical effect which is so dramatic, but it really shows that john has learned how to read the brain, how to use the information from the brain to drive a device. so that itself is a major insight. that you can make sense out of the action potential sequences in the brain. >> it really brings us to john's aspirations here. john krakauer of what you hope to do with stroke. why don't you outline what you are thinking about that. >> well, right so i think what follows then, i see, because the very same plasticity in these extreme cases where you are disconnected, where are you going to have to bypass the severed pathways and control an external device with this plas 'tis at this time, in patients who have stroke,
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for example where they still have some residual movement left, the question you want to ask is a similar one. can you somehow augment their plasticity in sort of enhance their recovery. and so there are a number of points to make about that. most patients after injury which are less extreme than what we just saw, recover to some degree and they recover most of the time within the first few months after stroke. but not completely. and we know from animal models that this seems to be a time window of plasticity that finishes after about three months in humans. about four weeks in ro dent models. so what we want to do is can we use technology to try and take advantage of in period of plas 'tis knit patients after stroke. so there are two kinds of technology that are being used increasingly now. so here is a real go robot. this is basically a robotic
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device that attaches to the effected limb of a patient after stroke. and what this robot can do is it can give varying degrees of assistance to the patient so that when they start to make a movement, the robot can give them 3-d assistance. and as they get better, as they begin to understand the kind of movement required of them you can begin to take away the robot's contribution so the idea would be to take patients early after stroke and with the use of a robot which can give you 100s if not thousands of reputation reputations-- repetitions we know large amounts for practice are required to actually interact with this plasticity to get recovery so what we need is some sort of device that doesn't get tired and can be programmed to give you hundreds of thousands of repetition and do it early. and these are what these robots can do. the second kind is to do something noninvasive unlike we just heard from john. when patients who are less severe, we don't necessarily think we have to put electrodes into the brain itself. we feel like we can actually
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stimulate the motor cortex, externally with either electrical or magnetic stimulation. here on this slide you can see this figure eight coil and what you do is you put current through that coil which then generates magnetic fields which are at right angles to the brain. and those magnetic fields induce current in neurons and stimulate a motor cortex. the other one instead of using magnetic fields you can use actually a 12 volt battery over the head and that also can actually increase excitable of motor cortex. these are two ways to augment activity and plasticity over targeted areas of the brain and a lot of studies are showing that these can increase and improve performance. so the dream would be the cocktail would be to take a patient early after stroke, in this window of plasticity, put them, hook them up to a robot and stimulate their brain at the same time. and potentially give them some sort of drug and with this cocktail, ramp up the amount of recovery that could occur in these patients early after stroke. >> let me go back. this notion of where you see
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the future of the kind of research you are doing with the deep brain stimulation. >> as you know, deep brain stimulation is now being exported if you will from the parkinson's tremor field so other movement disorders it has been successfully for distonya and other disorders characterized by excessive movement. but more strikingly, and i think remarkably for disorders, that really are psychiatric in nature, such as obsessive compulsive disorder, depression, and tourette's syndrome which say blend of movement and psychiatric disturbance. so i think the theme here is that we stimulate the motor circuit for movement disorders. we stimulate this emotional reward sdirt for treating these psychiatric disorders. and it seems to be more circuit specific than disease specific so we use
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the same targets, the same stimulation parameters for all of these conditions, granted that this is fairly large scale kind of stimulation. >> there is an interesting sociological point here, malion and that is that helen mayberg whom you had on this program recently introduced deep brain stimulation for depression. stimulating this area 25 that she found hyperactive. and here is a psychiatric illness that was treated successfully by a neurologist. and why is this so. why one psychiatrist doing this. and that is the cultural of the two fields are different. neurologists intrinsically from broker and vernica on have thought of anatomy, anatomy, anatomy, location, location, location. and psychiatrists have not thought in anatomical terms until just recently. >> the main thing, charlie, i would say about this technique is that it really has given renewed hope. >> enormous. >> for patients with psychiatric and neurologic
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disorders. >> the four people here have shown that in relatively short period of time, one or two generations, neurology has move ready from being a field in which with the exception of epilepsy nothing was really treated effectively to a point which really making major strides forward in treatment. i think this is a major, major advance. >> so pick up on terms it of -- >> so you might ask, i was talking about simple some systems, outing the fly and recreating the human disease in the fly. and you pite ask well, what is the point of that. well, the point is that you can then use the very powerful genetic tools that are available in the fly to define genes and gene pathways. and even drug compounds that can interfere with that. so for example, in parkinson's disease alpha cynucleon actually accumulates abnormalal so it looks like the protein
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undergos an abnormalal process clumping in the neurons. and this feature of abnormalal clumping of disease proteins is actually a feature of many different human neurodeagain rative diseases. so for example in alzheimer disease there are plaques and tangles. so this is sort of a common feature that the proteins seem to build up. and they clump abnormalally in the cells. and this is probably leading towards the toxicity, the path guinnessity so we have, and flies have very conserved pathways that are critical to help proteins take on their normal shape. so to prevent this kind of clumping. and these are called molecular chaperone pathways, so these are helper pathways that can help proteins fold properly. so we we considered if alpha cynucleon is causing toxicity potentially by clumping abnormalally what would happen if we gave the fly morse of these help procedure teens. so recall in the top panel, the fly has a set of nearons
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and in the middle panel those become compromised so that there are fewer cells staining if we express alpha cynuc lex, o n in those. but in the bottom panel we can see what happens when we add this helper protein this really great molecular chaper rone called hsp 7. -- 70. we restored the system back to internationalal. we no longer seen the compromise of these nearons. i should emphasize that hsp 70, this terrific chaper own works not only in this situation but it works in other fly neuroagain again rat-- deagain rative disease models which there are many and also in mouse mod ohls. so this is one example of where we sort of thought about what was happening. we stepped back from that and made a really good guess of what might be involved in the process. >> let me finally come back to you and tell me where the frontier is in terms of brain interface. >> sure. >> brain computer interface. >> well, it's not just brain
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computer interfaces. i think the future is to connect first i think for people who are unable to move and for whom we can't restore their full function, to connect them to external devices that are useful that can help them in their every day life. what many people don't appreciate is how devastating paralysis is especially the tetra palegia that sway, they can't do anything. so imagine if now you could control a very dextrous robotic arm that could get you a drink of water. this just shows now is not a paralyzed person but it is an able-bodied engineer, my colleague vogel and his, one of his coworkers. and they are showing very sophisticated robotic from the german space agency that he's controlling now with a real computer mouse with his actual arm underneath the table but it's showing now imagine a person could use their brain to control this and actually take a drink of water using this robotic arm
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and brain control. so we are actually under way doing this, asking our participants to try to accomplish this using a robotic limb. it will be slower than normal it won't be as dextrous as normal but we are very encouraged that we can have people once again interacting with their environment. but better than that i think, the next step for sus actually rewiring the brain back to the muscles with physical components. it is possible to put stimulators into the muscles. bring the brain signals to the muscles. and so therefore someone thinks and moves so our ultimate dream which is very far awaying. i'm not sure any of us at the table will see this, would be they we would be sitting here and one person would say yes, i had a spim cord injury. i've been rewired. i have several brap gaits, a bunch of wires, stimulators implanted but i can move like you or me and you can't distinguished. we'll go play tennis afterwards, you know, of course this is very far out. but we're coming. we've actually done in a simulation with a patient, the ability to make simple
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movements of their own arm. and this looks quite feasible. so i think you know, the future is very bright for a physical repair of the nervous system. >> i always like to do at the conclusion of these conversations is to ask the one question s it, what is the thing that you most, the question that you most like to see answered to see the realization of what you are talking about? >> well, this has the whole set of problems. currently our patients have a plug on their head they have a cable going to a big rack of computers. and we have the mystery of actually what the brain is doing. so i have the problem of wanting to do what the brain is actually doing. not what we think it's doing. i want to be able to make a device that will be hidden inside the body like a coke lear implant or cardiac pacemaker and take this chunk of computers and shrink them to something you might wear like an iphone in your pocket. those are our problems. >> what question do you most want answered. >> if you come from the point of view that i do which is to look at a really
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simple system, what you are seeing is emphasized, are the similarities and not the differences among different diseases. so we can model different diseases on the fly but they look more similar than different. so our idea that we are going after is that there might be common gene networks that underlie multiple different diseases. and if there are, then it means there might be gene nodes that we could attack for therapeutics. we would like to identify those gene networks that might tie multiple different diseases so that we can go after those in a therapeutic sense. >> so i have a comment and a. the comment is i think the great message that this show can put out is that the nervous system and neurological disease and neuroscience seems to benefit greatly from multilevel explanation. we've had genes, proteins, receptors. and i think that's not just about taste, even though eric made the great point that psychiatrists and
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neurologists seem to have their own preferred level of entry into understanding but the profound point is we need to attack all these levels and have research attacking all these levels and having everyone interact that my main comment. that is a profound thing about biology versus physics, for example. >> malion. >> my real question somewhere i started it this business. i was trying to understand the basal ganglia. i do not understand the basal ganglia. i understand how they can cause all kins of problems when they don't work. and how we can help with that, with these ways of modulating activity but i think we really don't understand exactly what we are doing and i think the evidence is pointing more and more towards something we talked about which is plasticity and learning. and i think this probably will be a more important and profitable venture than trying to figure out what we have been studying to this point.
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and it is a big topic but that's what i think the answers will be. >> my colleague. >> i would like to see the kinds of logic we've heard tonight around this table applied more extensively to psychiatrist-- psychiatry. i think psychiatry is lacking in emphasis on anatomy, on how different regions function, electrofi electrofisologicalically. and i think that kind of thinking needs to happen on a routine basis and one of the things we were discussing before we came in here was to what degree it ought to be a common training for neurologists and psychiatrists, at least for the first several years of their career. >> rose: is it psychiatry that is not receptive to this or what? >> some of my best friends are psychiatrists. these are cultures that have grown-up over a long period of time. and it's difficult to bring them together. although the leaders understand that this convergence is necessary. >> remarkable panel. when we reconvene here in
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two months, what will we talk about? >> we're going to speak about the role of the brain in decision-making. certain lesions of the brain make irresponsible as far as decision making is concerned. so emotion plays an important role in this. and disorders of emotion can interfere dramatically with your able to be a rational decision maker. so we are going to consider this next time. >> this is remarkable stuff. it really is. >> wonderful stuff. >> you just think about what we are learning. i mean it's like this most amazing organ and we are just beginning to understand it and we find out that we are building on the history of great people who had remarkable insight was any of the tool. >> absolutely right. >> that we have. >> this is the extraordinary thing. the major people like darwin and pen feel, they did extraordinary work with really primitive tools. being creative and bright helps. >> and it certainly has had that. thank you my friend. so there it is when we come back, the deciding brain.
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see you in september captioning sponsored by rose communications captioned by media access group at wgbh
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Charlie Rose
PBS September 3, 2010 11:00pm-12:00am PST

News/Business. (2010) The Charlie Rose Brain Series continues with the disordered brain. (CC) (Stereo)

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on 9/4/2010